In mammals, essential fatty acids, such as arachidonic acid, serve as substrates for cellular biological processes producing prostaglandins and the material SRS-A (Slow Reacting Substance of Anaphylaxis), the pathway to prostaglandins being catalyzed by prostaglandin synthetase and the pathway to SRS-A being catalyzed by lipoxygenase. The prostaglandin pathway leads to products of known beneficial function in mammals, while the SRS-A pathway produces products which have no known beneficial function in mammals.
After its cellular biosynthesis, SRS-A is released from the cell of origin and produces effects, such as bronchoconstriction, during an allergic response. There has been an ongoing need for agents that will specifically inhibit the synthesis of SRS-A by mammalian cells in order to prevent the release of SRS-A and the resulting asthmatic conditions thereto. In the past, methyl derivatives of arachidonic acid have been prepared. These derivatives relate to the inhibition of prostaglandin synthesis in order to treat disorders apparently arising therefrom.
In particular arachidonic acids methylated in the 2 or 3 position of the chain have been made by classical procedures wherein the intact arachidonic acid compound is methylated [Liang et al., Adv. Prost. Thrombox. Res. 6, 235 (1980)]. Also arachidonic acid analogs methylated in the 13 position have been disclosed by Yeh and Dawson, Tetrahedron Letters No. 49, pp. 4257-4260, (1977). This disclosure relates to compounds which have potential prostaglandin synthetase inhibitory activity.